Treatment of malaria restricted to laboratory-confirmed cases: a prospective cohort study in Ugandan children.

BACKGROUND: Presumptive treatment of malaria in febrile children is widely advocated in Africa. This may occur in the absence of diagnostic testing or even when diagnostic testing is performed but fails to detect malaria parasites. Such over-treatment of malaria has been tolerated in the era of inexpensive and safe monotherapy. However, with the introduction of new artemisinin-based combination therapy (ACT), presumptive treatment becomes economically and clinically less acceptable. METHODS: The risks and benefits of only treating children with microscopy confirmed malaria using a prospective cohort design were investigated. A representative sample of 601 children between one and 10 years of age were recruited from a census population in Kampala, Uganda and were followed for all of their health care needs in a study clinic. Standard microscopy was performed each time a child presented with a new episode of fever and antimalarial therapy given only if the blood smear was positive. RESULTS: Of 5,895 visits for new medical problems 40% were for febrile illnesses. Of the 2,359 episodes of new febrile illnesses, blood smears were initially reported as negative in 1,608 (68%) and no antimalarial therapy was given. Six of these initially negative smears were reported to be positive following quality control reading of all blood smears: four of these patients were subsequently diagnosed with uncomplicated malaria and two cleared their parasites without antimalarial treatment. Of the 1,602 new febrile illnesses in which the final blood smear reading was classified as negative, only 13 episodes (0.8%) were diagnosed with malaria in the subsequent 7 days. All 13 of these episodes of malaria were uncomplicated and were successfully treated. CONCLUSION: In this urban setting, malaria was responsible for only 32% of febrile episodes. Withholding antimalarial therapy in febrile children with negative blood smears was safe and saved over 1,600 antimalarial treatments in 601 children over an 18-month period. In the era of expensive ACT, directing resources towards improving diagnostic and treatment practices may provide a cost-effective measure for promoting rational use of antimalarial therapy

Clinical Performance of an Automated Reader in Interpreting Malaria Rapid Diagnostic Tests in Tanzania.

Parasitological confirmation of malaria is now recommended in all febrile patients by the World Health Organization (WHO) to reduce inappropriate use of anti-malarial drugs. Widespread implementation of rapid diagnostic tests (RDTs) is regarded as an effective strategy to achieve this goal. However, the quality of diagnosis provided by RDTs in remote rural dispensaries and health centres is not ideal. Feasible RDT quality control programmes in these settings are challenging. Collection of information regarding diagnostic events is also very deficient in low-resource countries. A prospective cohort of consecutive patients aged more than one year from both genders, seeking routine care for febrile episodes at dispensaries located in the Bagamoyo district of Tanzania, were enrolled into the study after signing an informed consent form. Blood samples were taken for thick blood smear (TBS) microscopic examination and malaria RDT (SD Bioline Malaria Antigen Pf/PanTM (SD RDT)). RDT results were interpreted by both visual interpretation and DekiReaderTM device. Results of visual interpretation were used for case management purposes. Microscopy was considered the "gold standard test" to assess the sensitivity and specificity of the DekiReader interpretation and to compare it to visual interpretation. In total, 1,346 febrile subjects were included in the final analysis. The SD RDT, when used in conjunction with the DekiReader and upon visual interpretation, had sensitivities of 95.3% (95% CI, 90.6-97.7) and 94.7% (95% CI, 89.8--97.3) respectively, and specificities of 94.6% (95% CI, 93.5--96.1) and 95.6% (95% CI, 94.2--96.6), respectively to gold standard. There was a high percentage of overall agreement between the two methods of interpretation. The sensitivity and specificity of the DekiReader in interpretation of SD RDTs were comparable to previous reports and showed high agreement to visual interpretation (>98%). The results of the study reflect the situation in real practice and show good performance characteristics of DekiReader on interpreting malaria RDTs in the hands of local laboratory technicians. They also suggest that a system like this could provide great benefits to the health care system. Further studies to look at ease of use by community health workers, and cost benefit of the system are warranted

Information Technology as a Mechanism for Educational Transformations in a Changing Society

Education is a definite and ground-breaking channel for a high standard of living, an opportunity for intellectual interactions, social networking amongst current academic professionals, college and university graduates, at local, state, and community. The primary purpose of life-long education is to promote personal and professional development, and advancement of the national and world economy. Ancient times support the premise that after continued self-regulating attempts, the time has come for current and future graduates, professionals, and the entire education community to focus on the primacy of computer information technology, which has widened human access to vital data, video, and information transmission and communication, also created an irreversible phenomenon in instruction and learning endeavors, and continues to serve as the best medium for multiple sources of information and communication. The emergence of computer information technology has equally created a wide range of opportunities for greater production; doing away with the lingering global language barriers, and creating a working podium in the academic and political world. It is a proven tenet that the continued use of computer information technology and associated devices such as the Internet, mobile telephones, and electronic mail for data, information transmission, and communication has improved the standard of living and enhanced the exchange of ideas, effective method of learning endeavours, a decrease in alarming attrition rate of students dropping out of the degree programmes and improvement in academic performance

Scale-up of Malaria Rapid Diagnostic Tests and Artemisinin-Based Combination Therapy: Challenges and Perspectives in Sub-Saharan Africa.

Guido Bastiaens and colleagues describe barriers to achieving scale-up and appropriate use of rapid diagnostic tests and artemisinin-based combination therapy for malaria in sub-Saharan Africa. Please see later in the article for the Editors' Summary

Longitudinal study of urban malaria in a cohort of Ugandan children: description of study site, census and recruitment

BACKGROUND: Studies of malaria in well-defined cohorts offer important data about the epidemiology of this complex disease, but few have been done in urban African populations. To generate a sampling frame for a longitudinal study of malaria incidence and treatment in Kampala, Uganda, a census, mapping and survey project was conducted. METHODS: All households in a geographically defined area were enumerated and mapped. Probability sampling was used to recruit a representative sample of children and collect baseline descriptive data for future longitudinal studies. RESULTS: 16,172 residents living in 4931 households in a densely-populated community (18,824 persons/km(2)) were enumerated. A total of 582 households were approached with at least one child less than 10 years of age in order to recruit 601 children living in 322 households. At enrollment, 19% were parasitaemic, 24% were anaemic, 43% used bednets, and 6% used insecticide-treated nets. Low G6PD activity (OR = 0.33, P = 0.009) and bednet use (OR = 0.64, P = 0.045) were associated with a decreased risk of parasitaemia. Increasing age (OR = 0.62 for each year, P < 0.001) and bednet use (OR = 0.58, P = 0.02) were associated with a decreased risk of anaemia CONCLUSION: Detailed surveys of target populations in urban Africa can provide valuable descriptive data and provide a sampling frame for recruitment of representative cohorts for longitudinal studies. Plans to use a multi-disciplinary approach to improve the understanding of the distribution and determinants of malaria incidence and response to therapy in this population are discussed

Incidence of Malaria and Efficacy of Combination Antimalarial Therapies over 4 Years in an Urban Cohort of Ugandan Children

Combination therapies are now recommended to treat uncomplicated malaria. We used a longitudinal design to assess the incidence of malaria and compare the efficacies of 3 combination regimens in Kampala, Uganda.Children aged 1-10 years were enrolled from randomly selected households in 2004-05 and 2007, and were followed at least monthly through 2008. Insecticide-treated bednets (ITNs) were provided in 2006. Children were randomized upon their first episode, and then treated for all episodes of uncomplicated malaria with amodiaquine/sulfadoxine-pyrimethamine (AQ/SP), artesunate/amodiaquine (AS/AQ), or artemether/lumefantrine (AL). Risks of parasitological failure were determined for each episode of uncomplicated malaria and clinical parameters were followed. A total of 690 children experienced 1464 episodes of malaria. 96% of these episodes were uncomplicated malaria and treated with study drugs; 94% were due to Plasmodium falciparum. The rank order of treatment efficacy was AL > AS/AQ > AQ/SP. Failure rates increased over time for AQ/SP, but not the artemisinin-based regimens. Over the 4-year course of the study the prevalence of asymptomatic parasitemia decreased from 11.8% to 1.4%, the incidence of malaria decreased from 1.55 to 0.32 per person year, and the prevalence of anemia (hemoglobin <10 gm/dL) decreased from 5.9% to 1.0%. No episodes of severe malaria (based on WHO criteria) and no deaths were seen.With ready access to combination therapies and distribution of ITNs, responses were excellent for artemisinin-containing regimens, severe malaria was not seen, and the incidence of malaria and prevalence of parasitemia and anemia decreased steadily over time.isrctn.org ISRCTN37517549

Time To Move from Presumptive Malaria Treatment to Laboratory-Confirmed Diagnosis and Treatment in African Children with Fever

Background to the debate: Current guidelines recommend that all fever episodes in African children be treated presumptively with antimalarial drugs. But declining malarial transmission in parts of sub-Saharan Africa, declining proportions of fevers due to malaria, and the availability of rapid diagnostic tests mean it may be time for this policy to change. This debate examines whether enough evidence exists to support abandoning presumptive treatment and whether African health systems have the capacity to support a shift toward laboratory-confirmed rather than presumptive diagnosis and treatment of malaria in children under five

Presumptive treatment with sulphadoxine-pyrimethamine versus weekly chloroquine for malaria prophylaxis in children with sickle cell anaemia in Uganda: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Malaria carries high case fatality among children with sickle cell anaemia. In Uganda, chloroquine is used for prophylaxis in these children despite unacceptably high levels of resistance. Intermittent presumptive treatment with sulphadoxine-pyrimethamine (SP) has shown great potential for reducing prevalence of malaria and anaemia among pregnant women and infants.</p> <p>Objective</p> <p>To compare the efficacy of monthly SP presumptive treatment, versus weekly chloroquine for malaria prophylaxis in children attending the Sickle Cell Clinic, Mulago Hospital.</p> <p>Methods</p> <p>Two hundred and forty two children with sickle cell anaemia were randomized to presumptive treatment with SP or weekly chloroquine for malaria prophylaxis. Active detection of malaria was made at each weekly visit to the clinic over one month. The primary outcome measure was the proportion of children with one malaria episode at one month follow-up. The secondary outcome measures included malaria-related admissions and adverse effects of the drugs.</p> <p>Results</p> <p>Ninety-three percent (114/122) of the children in the chloroquine group and 94% (113/120) in the SP group completed one month follow up. SP reduced prevalence of malaria by 50% compared to chloroquine [OR = 0.50, (95% CI 0.26-0.97)]; p = 0.042. Six percent (7/122) of the children receiving weekly chloroquine had malaria related admissions compared to 2.5% (3/120) on presumptive treatment with SP. No serious drug effects were reported in both treatment groups</p> <p>Conclusion</p> <p>Presumptive treatment with SP was more efficacious than weekly chloroquine in reducing prevalence of malaria in children with sickle cell anaemia. Continued use of chloroquine for malaria chemoprophylaxis in children with sickle cell anaemia in Uganda does not seem to be justified.</p> <p>Clinical Trials Registration</p> <p>ClinicalTrials.gov Identifier: NCTOO124267</p

Can changes in malaria transmission intensity explain prolonged protection and contribute to high protective efficacy of intermittent preventive treatment for malaria in infants?

BACKGROUND: Intermittent preventive (or presumptive) treatment of infants (IPTi), the administration of a curative anti-malarial dose to infants whether or not they are known to be infected, is being considered as a new strategy for malaria control. Five of the six trials using sulphadoxine-pyrimethamine (SP) for IPTi showed protective efficacies (PEs) against clinical malaria ranging from 20.1 - 33.3% whilst one, the Ifakara study, showed a protective efficacy of 58.6%. MATERIALS AND METHODS: The possible mechanisms that could explain the differences in the reported PE of IPTi were examined by comparing output from a mathematical model to data from the six published IPTi trials. RESULTS: Under stable transmission, the PE of IPTi predicted by the model was comparable with the observed PEs in all but the Ifakara study (ratio of the mean predicted PE to that observed was 1.02, range 0.39 - 1.59). When a reduction in the incidence of infection during the study was included in the model, the predicted PE of IPTi increased and extended into the second year of life, as observed in the Ifakara study. CONCLUSION: A decrease in malaria transmission during the study period may explain part of the difference in observed PEs of IPTi between sites and the extended period of protection into the second year of life observed in the Ifakara study. This finding of continued benefit of interventions in settings of decreasing transmission may explain why rebound of clinical malaria was absent in the large scale trials of insecticide-treated bed nets

Accuracy of Rapid Tests for Malaria and Treatment Outcomes for Malaria and Non-Malaria Cases among Under-Five Children in Rural Ghana

BACKGROUND: WHO now recommends test-based management of malaria across all transmission settings. The accuracy of rapid diagnostic test (RDT) and the outcome of treatment based on the result of tests will influence acceptability of and adherence to the new guidelines. METHOD: We conducted a study at the Kintampo hospital in rural Ghana to evaluate the performance of CareStart, a HRP-2 based RDT, using microscopy as reference. We applied IMCI treatment guidelines, restricted ACT to RDT-positive children and followed-up both RDT-positive (malaria) and RDT-negative (non-malaria) cases over 28 days. RESULTS: 436 children were enrolled in the RDT evaluation and 391 (children with haemoglobin >8.0 gm/dl) were followed-up to assess treatment outcomes. Mean age was 25.4 months (s.d. 14.6). Sensitivity and specificity of the RDT were 100.0% and 73.0% respectively. Over the follow-up period, 32 (18.5%) RDT-negative children converted to positive, with 7 (4.0%) of them presenting with fever. More children in the non-malaria group made unscheduled visits than children in the malaria group (13.3% versus 7.7%) On all scheduled follow-up visits, proportion of children having a temperature higher than that recorded on day 0 was higher in the non-malaria group compared to the malaria group. Reports of unfavourable treatment outcomes by caregivers were higher among the non-malaria group than the malaria group. CONCLUSIONS: The RDT had good sensitivity and specificity. However a minority of children who will not receive ACT based on RDT results may develop clinical malaria within a short period in high transmission settings. This could undermine caregivers' and health workers' confidence in the new guidelines. Improving the quality of management of non-malarial febrile illnesses should be a priority in the era of test-based management of malaria. TRIAL REGISTRATION: ClinicalTrials.gov NCT00832754